Cryptococcal meningitis (CM) results from infection by the encapsulated yeasts Cryptococcus neoformans and Cryptococcus gattii and is observed almost exclusively in immune-compromised individuals. The enormous population of HIV-infected people in sub-Saharan Africa (estimated to be more than 20 million), with inadequate access to antiretroviral therapy, is highly susceptible to this disease. The most common drug treatment for CM in this patient population is high-dose fluconazole monotherapy, but it achieves only a 40 percent survival rate after 10 weeks of treatment. A more potent anti-fungal drug that can be given orally once a day would likely provide a significant improvement in survival for this neglected population. This project includes pre-clinical Investigational New Drug (IND)-enabling studies that will evaluate VT-1129 as a novel, oral, stand-alone drug candidate for the treatment of CM. TRND researchers conducted validation studies for the lead compound, VT-1129, including pharmacokinetic, efficacy and toxicology studies in rodents and non-rodents, enabling selection of an optimal dosing regimen to balance efficacy and safety. The TRND team optimized a synthetic process for scaled-up production of drug at a low cost that will support treatment of patients in the developing world. Additional collaborative studies were completed with the Centers for Disease Control and Prevention (CDC) to test the in vitro efficacy of the molecule against 400 fungal strains from Africa. This TRND support enabled Viamet to successfully raise venture capital funding to continue development of the de-risked candidate.